DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed adenocarcinoma of the colon or rectum

  • Locally advanced (unresectable) or metastatic disease

    • Patients with resected primary tumors who have documented metastases are eligible

    • Separate histological or cytological confirmation is not required from patients with a history of colorectal cancer (previously treated by surgical resection) who have now developed radiological or clinical evidence of metastatic disease, unless 1 of the following is true:

      • An interval of > 5 years has elapsed between the primary surgery and the development of metastatic disease
      • The primary cancer was stage I

• The intent of this treatment must be indicated as follows:

  • Palliative or neoadjuvant treatment with the potential for resection of all sites of metastatic disease
• At least 1 paraffin block of previously resected primary tumor or tumor deposit available
• Patients must have a wildtype K-ras gene
• No known CNS metastases or carcinomatous meningitis

PATIENT CHARACTERISTICS:

Performance status

• ECOG 0-1

Life expectancy

• Not specified

Hematopoietic

• Granulocyte count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Hemoglobin ≥ 9.0 g/dL (transfusion allowed)
• No history of significant bleeding events (e.g., hemoptysis or upper or lower gastrointestinal bleeding) within the past 6 months unless the source of bleeding has been resected

Hepatic

• Bilirubin ≤ 1.5 mg/dL
• Albumin ≥ 2.5 g/dL

• No evidence of Gilbert's syndrome for patients assigned to receive FOLFIRI chemotherapy

  • Gilbert's syndrome allowed for patients assigned to receive FOLFOX chemotherapy

Renal

• Creatinine ≤ 1.5 times upper limit of normal

• Protein < 1+ by urinalysis

  • Protein < 1 g by 24-hour urine collection for patients with protein ≥ 2+ by urinalysis

Cardiovascular

• No arterial thromboembolic event within the past 6 months, including any of the following:

  • Myocardial infarction
  • Transient ischemic attack
  • Cerebrovascular accident
  • Unstable angina or angina requiring surgical or medical intervention
• No uncontrolled hypertension (i.e., blood pressure ≥ 160/90 on a regimen of antihypertensive therapy)
• No New York Heart Association class II-IV congestive heart failure
• No clinically significant peripheral artery disease (i.e., claudication on less than 1 block)

Pulmonary

• No interstitial pneumonia
• No extensive or symptomatic interstitial fibrosis of the lung
• No pleural effusion or ascites that causes ≥ grade 2 dyspnea

Gastrointestinal

• No gastrointestinal perforation within past year

• No uncontrolled, predisposing colonic or small bowel disorder (i.e., > 3 watery or soft stools daily for patients without a colostomy or ileostomy)

  • Patients with a colostomy or ileostomy are eligible at the discretion of the investigator

Neurologic

• No sensory peripheral neuropathy ≥ grade 2 for patients assigned to receive FOLFOX chemotherapy
• No uncontrolled seizure disorder
• No active neurological disease

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for at least 2-6 months after completion of study treatment
• No serious nonhealing wound, ulcer, or bone fracture
• No known hypersensitivity to Chinese hamster ovary cell products or recombinant human or murine antibodies
• No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No prior agents that target vascular endothelial growth factor (VEGF) or EGF receptors including protein products, monoclonal antibodies, or antisense therapies
• No prior bevacizumab or cetuximab
• No concurrent prophylactic filgrastim (G-CSF), pegfilgrastim, or sargramostim (GM-CSF)

Chemotherapy

• See Radiotherapy
• More than 12 months since prior adjuvant chemotherapy (≤ 6 months in duration) that included fluorouracil alone or in combination with oxaliplatin or irinotecan hydrochloride
• No prior regional chemotherapy (e.g., hepatic arterial infusion)
• No other concurrent chemotherapy

Endocrine therapy

• No concurrent hormonal therapy except steroids for adrenal failure, hormones for noncancer-related conditions (e.g., insulin for diabetes), or intermittent dexamethasone as an antiemetic

Radiotherapy

• Prior radiotherapy with radiosensitizing chemotherapy allowed
• Prior standard adjuvant chemoradiotherapy for rectal cancer allowed
• At least 4 weeks since prior radiotherapy
• No prior radiotherapy to > 25% of bone marrow
• No concurrent palliative radiotherapy except whole brain irradiation for documented CNS disease

Surgery

• See Disease Characteristics
• At least 4 weeks since prior major surgery

• At least 2 weeks since prior minor surgery

  • Insertion of a vascular access device is not considered a prior surgery
• Recovered from all prior surgery

Other

• At least 4 weeks since prior itraconazole or ketoconazole
• No prior tyrosine kinase inhibitor therapy
• No prior systemic treatment for advanced or metastatic colorectal cancer
• No concurrent aprepitant

• Concurrent full-dose anticoagulation (i.e., warfarin) allowed provided all of the following criteria are met:

  • In-range INR (usually 2-3) on a stable dose of oral anticoagulant or stable dose of low molecular weight heparin
  • No active bleeding
  • No pathological condition with a high risk of bleeding (e.g., tumor involving major vessels or known varices)
• Concurrent antiplatelet agents allowed
• Concurrent daily prophylactic aspirin or anticoagulation for atrial fibrillation allowed