• Progression-free survival [ Designated as safety issue: No ]
  

• Duration of disease control [ Designated as safety issue: No ]
  
• Overall survival [ Designated as safety issue: No ]
  
• Response rates [ Designated as safety issue: No ]
  
• Chemotherapy-free interval [ Designated as safety issue: No ]
  
• Salvage surgery rates [ Designated as safety issue: No ]
  
• Tolerability as measured by NCI CTCAE v3.0 [ Designated as safety issue: Yes ]
  
• Quality of life as measured by Functional Assessment of Cancer Therapy Neurotoxicity Module v4.0 and European Quality of Life questionnaire (EQ-5D) scale at baseline, courses 4 and 6, and every 2 months thereafter [ Designated as safety issue: Yes ]
  
• Pharmacogenetics and pharmacoeconomics [ Designated as safety issue: No ]
  

DISEASE CHARACTERISTICS:

• Histologically proven metastatic adenocarcinoma of colon or rectum

  • Documented inoperable disease (i.e., not suitable for complete carcinological surgical resection)
• Measurable lesion as assessed by CT scan or MRI in at least one dimension (longest diameter to be recorded) ≥ 20 mm with conventional CT scan or ≥ 10 mm with spiral CT scan
• No history or evidence upon physical examination of CNS disease (e.g., non-irradiated CNS metastasis, seizure not controlled with standard medical therapy, or history of stroke) unless adequately treated
• No exclusive bone metastasis
• No symptomatic ascites or pleural effusion not evacuated prior to entry into the study

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2
• WBC ≥ 1,500/mm^3
• Platelets ≥ 100,000/mm^3
• Hemoglobin > 9 g/dL (may be transfused to maintain or exceed this level)
• INR ≤ 1.5
• PPT < 1.5 times upper limit of normal (ULN)
• Creatinine < 1.5 mg/dL
• Creatinine clearance > 30 mL/min
• Proteinuria < 2+ by dipstick OR ≤ 1 g of protein on 24-hr urine collection
• Bilirubin < 1.5 times ULN
• Alkaline phosphatase < 3 times ULN
• No peripheral sensory neuropathy
• Negative pregnancy test
• Fertile patients must use effective means of contraception (oral contraceptives, intrauterine contraceptive device, barrier method of contraception in conjunction with spermicidal jelly, or surgically sterilization)
• No significant traumatic injury within the past 28 days
• Fully healed wounds
• No total or partial bowel obstruction
• No uncontrolled hypercalcemia
• No other concomitant or previous malignancy, except adequately treated in situ carcinoma of the uterine cervix or basal or squamous cell carcinoma of the skin or cancer in complete remission for < 5 years
• No peripheral neuropathy ≥ grade 1
• No other serious nonmalignant disease
• No pre-existing lung disease (in particular chronic obstructive lung disease, pleural effusion, lymphangitis carcinomatosis, or interstitial syndrome)

• No clinically significant (i.e. active) cardiovascular disease including any the following:

  • Cerebrovascular accidents in the past 6 months
  • Myocardial infarction in the past year
  • Unstable angina
  • New York Heart Association grade II or greater congestive heart failure
  • Serious cardiac arrhythmia requiring medication
  • Uncontrolled hypertension
• No evidence of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates use of an investigational drug
• Not at high risk of treatment complications
• No evidence of bleeding diathesis or coagulopathy
• No serious, non-healing wound, ulcer, or bone fracture
• No known allergy to any excipients of study drugs
• No significant ophthalmologic abnormality, especially severe dry eye syndrome, keratoconjunctivitis sicca, Sjögren's syndrome, severe exposure keratitis or any other disorder likely to increase the risk of corneal epithelial lesions (the use of contact lenses is not recommended during the study)

PRIOR CONCURRENT THERAPY:

• No previous chemotherapy and/or immunotherapy for metastatic disease

  • More than 6 months since prior adjuvant chemotherapy (2 years if oxaliplatin or irinotecan was received as adjuvant therapy)
• No prior palliative chemotherapy and/or immunotherapy for metastatic disease
• More than 28 days since prior major surgical procedure or open biopsy
• More than 10 days since prior use of full-dose oral or parenteral anticoagulants for therapeutic purposes
• No concurrent full-dose oral or parenteral anticoagulants for therapeutic purposes
• No concurrent chronic, daily treatment with aspirin (> 325 mg/day)
• No other concurrent antitumor treatment
• No participation in another clinical trial with any investigational drug within 30 days prior to randomization or during study participation
• No other concurrent agents known to have anticancer activity
• No concurrent radiotherapy
• No concurrent treatments that could cause an interstitial pulmonary syndrome (e.g., thoracic radiotherapy, beta blockers, nonsteroidal anti-inflammatory drugs, or bleomycin)