Inclusion Criteria:

• Histologically or cytologically confirmed adenocarcinoma of the colon or rectum.
• Metastatic disease consistent with colorectal adenocarcinoma. Stage M1, and not amenable to curative surgery. Subjects with only locally persistent or only locally recurrent disease are not eligible.
• No prior systemic therapy for metastatic cancer. Prior adjuvant chemotherapy with a 5-FU-based treatment regimen not containing oxaliplatin or irinotecan is acceptable after a treatment-free interval of at least 6 months.
• ECOG performance score (PS) of 0 or 1.
• Life expectancy more than 3 months.
• Subject must have measurable disease, defined by the RECIST criteria.
• At least 28 days must have elapsed since prior surgery except venous access device placement.
• At least 28 days must have elapsed since prior radiotherapy.
• At least 28 days must have elapsed since a prior investigational agent.
• Absolute neutrophil count (ANC) equal to or greater than 1.5 x 10^9/L.
• Platelet count equal to or greater than 100 x 10^9/L.
• Hemoglobin equal or greater than 10g/dL (must be obtained at least 3 days after any transfusion).
• Serum AST and ALT levels less than or equal to 2.5 times upper limit of normal (ULN) or less than 5 times ULN if liver involvement is present.
• Serum bilirubin of less than or equal to 1.5 ULN.
• Serum creatinine of less than or equal to ULN.
• Women of childbearing potential must have a negative pregnancy test (serum or urine beta HCG).
• All subjects must agree to use appropriate birth control methods while on study and for 1 month after completion of study chemotherapy.

Exclusion Criteria:

• Concurrent use of EGFR inhibitors or anti-VEGF agents.
• No clinically significant obstructive symptoms or intestinal bleeding.
• Significant chronic or recent acute gastrointestinal disorder with diarrhea as a major symptom (e.g. Crohn's disease, ulcerative colitis, malabsorption syndrome, Grade 2+ diarrhea of any etiology at baseline).
• History of serious cardiac disease, defined as myocardial infarction within six months of enrollment, congestive heart failure classified by the New York Heart Association as class III or IV, uncontrolled cardiac arrhythmias, poorly controlled or unstable angina, or electrocardiographic evidence of acute ischemia.
• Clinical evidence of brain metastases or central nervous system disease.
• Symptomatic peripheral neuropathy (equivalent to Grade 2 or higher CTCAE toxicity criteria).
• Uncontrolled intercurrent illness (e.g. active infection).
• Pregnant or nursing.
• Serious medical or psychiatric illness that could potentially interfere with the completion of study treatment according to this protocol.
• Malignancy other than colorectal carcinoma within the past 5 years, except, curatively treated, superficial skin cancer or carcinoma in situ of the cervix or breast.