Inclusion Criteria:

• Patients must have histological or cytological confirmed metastatic colorectal cancer.
• Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >20 mm with conventional techniques or as >10 mm with spiral CT scan.
• No prior chemotherapy in the metastatic setting (prior fluorouracil chemotherapy, if administered in the adjuvant setting, and if more than 6 months has passed since the completion of therapy, is allowable). Prior adjuvant radiation therapy allowable provided no greater than 30% total bone marrow included in the field (must be more than 6 weeks since completion of radiation therapy.
• Subject must be 18 years or older
• Life expectancy greater than 12 weeks.
• ECOG performance status <2 (Karnofsky >60%).
• Patients must have normal organ and marrow function as defined as: leukocytes >3,000/mcL; absolute neutrophil count >1,500/mcL; Platelets >100,000/mcL; total bilirubin within normal institutional limits; AST(SGOT)/ALT (SGPT) <2.5 X institutional upper limit of normal; Creatinine within normal institutional limits and Creatinine clearance (estimated by Cockcroft-Gault equation)>50-mL/min/1.73 m2 for patients with creatinine levels above institutional normal
• Has a negative serum or urine pregnancy test within 7 days prior to initiation of therapy (female patients of childbearing potential).
• Woman of childbearing potential with either a positive or no pregnancy test at baseline. (Postmenopausal woman must have been amenorrheic for at least 12 months to be considered of non-childbearing potential). Patients will agree to continue contraception for 30 days from the date of the last study drug administration
• Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

• Prior therapy for MCRC in the metastatic setting.
• Patients may not be receiving any other investigational agents.
• Patients with known brain metastases will be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
• Grade 2 or greater peripheral neuropathy.
• Prior unanticipated severe reaction to fluoropyrimidine therapy, or known sensitivity to 5-fluorouracil.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. Clinically significant cardiac disease (e.g. congestive heart failure, symptomatic coronary artery disease and cardiac arrhythmias not well controlled with medication) or myocardial infarction within the last 12 months.
• Pregnant and nursing women are excluded from this study. Women / men of childbearing potential not using a reliable and appropriate contraceptive method.
• Because patients with immune deficiency are at increased risk of lethal infections when treated with marrow-suppressive therapy, HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study because of possible pharmacokinetic interactions with Oxaliplatin and Irinotecan or other agents administered during the study.
• Major surgery within 4 weeks of the start of study treatment, without complete recovery.
• Lack of physical integrity of the upper gastrointestinal tract or malabsorption syndrome.
• History of clinically significant interstitial lung disease and/or pulmonary fibrosis.
• History of persistent neurosensory disorder including but not limited to peripheral neuropathy
• Treatment for other carcinomas within the last five years, except cured non-melanoma skin and treated in-situ cervical cancer.
• Participation in any investigational drug study within 4 weeks preceding the start of study treatment.
• Any prior platinum based therapy