Inclusion Criteria:

• Histologically or cytologically confirmed metastatic or recurrent colorectal tumors with no previous treatment for advanced disease.
• Age greater than or equal to 18 years
• SWOG performance status 0-1.
• At least one measurable lesion according to the RECIST criteria which has not been irradiated (i.e. newly arising lesions in previously irradiated areas are accepted). Minimum indicator lesion size: > 10 mm measured by spiral CT or >20mm measured by conventional techniques.
• Have a negative serum pregnancy test within 7 days prior to initiation of chemotherapy (female patients of childbearing potential).
• Availability of tumor biopsy (paraffin embedded or fresh frozen) at the time of diagnosis and/or prior to study entry is required.
• Patients must agree to have a 20 cc blood sample drawn in addition to routine labs with each cycle of chemotherapy.

Exclusion Criteria:

• Pregnant or lactating woman.
• Life expectancy < 3 months.
• Serious, uncontrolled, concurrent infection(s) or illness(es)
• Any prior oxaliplatin treatment, with the exception of adjuvant therapy given > 12 months prior to the beginning of study therapy
• Prior unanticipated severe reaction to fluoropyrimidine therapy, known hypersensitivity to 5-fluorouracil, or known DPD deficiency
• Prior unanticipated severe reaction or hypersensitivity to platinum based compounds.
• Treatment for other carcinomas within the last five years, except cured non-melanoma skin and treated in-situ cervical cancer.
• Current, recent (within 4 weeks of first infusion on this study) or planned participation in an investigational drug study.
• Clinically significant cardiac disease (e.g. congestive heart failure, symptomatic coronary artery disease and cardiac arrhythmias not well controlled with medication) within the last 6 months.
• History of clinically significant interstitial lung disease and/or pulmonary fibrosis.
• History of persistent neurosensory disorder including but not limited to peripheral neuropathy.
• Presence of central nervous system or brain mets.
• Major surgery, open biopsy, or significant traumatic injury within 28 days prior to Day 0, or anticipation of need for major surgical procedure during the course of the study.
• Lack of physical integrity of the upper gastrointestinal tract or malabsorption syndrome.

• Any of the following laboratory values:

  • Abnormal hematologic values (neutrophils < 1.5 x 109/L, platelet count < 100 x 109/L)
  • Urine protein: creatinine ratio >/= 1.0 Impaired renal function with estimated creatinine clearance < 30 ml/min as calculated with Cockroft et

Gault equation:

• Serum bilirubin > 1.5 x upper normal limit. ALT, AST > 2.5 x upper normal limit (or > 5 x upper normal limit in the case of liver metastases)

• Alkaline phosphatase > 2.5 x upper normal limit (or > 5 x upper normal limit in the case of liver metastases or > 10 x upper normal limit in the case of bone disease)

  • Minor surgical procedures, fine needle aspirations or core biopsies within 7 days prior to Day 0
  • Blood pressure > 150/100 mmHg
  • Unstable angina
  • New York Heart Association (NYHA) Grade II or greater congestive heart failure
  • History of myocardial infarction or stroke within 6 months
  • Clinically significant peripheral vascular disease
  • Evidence of bleeding diathesis or coagulopathy
  • History of abdominal fistula, gastrointestinal perforation or intraabdominal abscess within 28 days prior to Day 0.
  • Serious, non-healing wound, ulcer or bone fracture
  • Carcinoma of any histology in close proximity to a major vessel, cavitation or history of hemoptysis.
  • Completion of previous adjuvant chemotherapy regimen < four weeks prior to the start of study treatment (within six weeks of study treatment for mitomycin C and nitroureas), or with related toxicities unresolved prior to the start of study treatment.