INCLUSION CRITERIA:

A patient will be eligible for inclusion in this study if s/he meets all of the following criteria:

• Has histologically or cytologically confirmed colorectal cancer with metastatic disease documented on diagnostic imaging studies
• Has measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) with minimum lesion size equal to or more than twice the slice thickness of the imaging study used. See protocol for the definition of measurable disease. Previously irradiated lesions will be considered evaluable as long as they have progressed since radiation. Previously irradiated lesions can not be the only measurable disease.
• Has disease other than that limited to surgically resectable liver-only or lung-only metastatic disease
• Has not received prior chemotherapy and/or biotherapy for metastatic disease
• Has not received oxaliplatin, bevacizumab, or cetuximab in the adjuvant setting
• May have received 5-FU, leucovorin, and/or irinotecan in the adjuvant setting, however they must have remained free of disease recurrence (including free of abnormal CEA level) for 1- year or more from the date of completion of last adjuvant treatment
• Is >18 years of age
• Has Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
• Has normal organ and marrow function. (See Protocol)
• If fertile, patient (male or female) has agreed to use an acceptable method of birth control to avoid pregnancy for the duration of the study and for a period of at least 2 months thereafter
• Is not pregnanant of breast feeding
• Has paraffin tissue block(s) or 12 (minimum) unstained slides available, from either primary of metastatic site of colorectal cancer, for the assessment of potential predictive markers related to the EGFR, VEGF, DNA repair, and fluoropyrimidine catabolism pathways. The tissue block is the preferred specimen. If no block is available, then slides (typically 7 to 10 um sections, air dried on uncharged slides) may be sent. Appendix IX has central laboratory information. Note: if a block is sent, slides will be prepared and the remainder of the block will be returned to the source, slides will not be returned
• Has the ability to understand and the willingness to have signed a Patient Informed Consent Form
• Has signed a Patient Informed Consent Form
• Has signed a Patient Authorization Form (HIPAA) or other appropriate HIPAA Authorization Form

EXCLUSION CRITERIA:

A patient will be excluded from this study if s/he meets any of the following criteria:

• Has had prior chemotherapy for metastatic colorectal cancer
• Has received any prior treatment with oxaliplatin, bevacizumab, or cetuximab in the adjuvant treatment of their colorectal cancer
• Is currently receiving any other investigational anticancer agents or has participated in an experimental drug study within the past 4 weeks
• Has known CNS or brain metastases
• Has a history of primary CNS tumors, seizures not well-controlled with standard medical therapy, or stroke
• Has sustained hypertension, as characterized by persistent blood pressures greater than 150/100 despite medical management
• Has New York Heart Association (NYHA) Grade II or greater congestive heart failure (see protocol appendix) or has had angioplasty or placement of coronary stents within the past 6 months
• Has clinically significant peripheral vascular disease
• Has a history of serious allergic reactions attributed to compounds of similar chemical or biologic composition to bevacizumab, cetuximab, oxaliplatin, fluorouracil, leucovorin, or other agents used in the study
• Has received prior cetuximab or other EGFR-directed therapy, or a history of prior anti-cancer murine or chimeric monoclonal antibody therapy; prior humanized and human monoclonal antibody therapy is also excluded).
• Has received prior treatment with bevacizumab or other agents specifically targeting VEGF or VEGF receptors
• Has uncontrolled intercurrent illness including, not limited to, ongoing or active infection requiring parenteral antibiotics, symptomatic congestive heart failure, uncontrolled hypertension, clinically significant cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements in the opinion of the Investigator/Treating Physician
• Has a serious or non-healing active wound ulcer, or active bone fracture
• Has had a major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 1 of protocol treatment
• Minor surgical procedures such as fine needle aspirations or core biopsies within 7 days prior to Day 1
• Has a history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to Day 1
• Has current or recent use of a thrombolytic agent within last 30 days. Use for clearance of central line catheter is permitted.
• Has evidence of bleeding diathesis (disorder) or clinically significant coagulopathy (Note that deep venous thrombosis is not regarded as a reason for exclusion from this trial)
• Has a known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies
• Has a known history of arterial thromboembolic events, including transient ischemic attack, cerebrovascular accident, unstable angina, or myocardial infarction within 6 months
• Urine protein:creatinine ratio greater than 1.0 at screening (see protocol)
• Is a pregnant or lactating woman
• Is known to be HIV positive or is receiving combination anti-retroviral therapy
• Is unable to comply with requirements of study