Inclusion Criteria:

• No prior chemotherapy for metastatic disease.
• Histologically proven mCRC.
• Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) criteria.
• Age: at least 18 years.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at study entry (see Appendix 2).

• Adequate bone marrow, liver and renal function at study entry as assessed by the following:

  • Hemoglobin >9.0 g/dL.
  • Absolute neutrophil count (ANC) ≥1500/mm3.
  • Platelet count ≥100,000/mm3.
  • Total bilirubin ≤1.5 times (×) upper limit of normal (ULN).
  • Alanine transaminase (ALT) and asparatate transaminase (AST) ≤2.5 × ULN (≤5 × ULN for patients with liver involvement).
  • Creatinine ≤1.5 × ULN.
• International normalized ratio (INR) <1.5 or a prothrombin (PT)/partial thromboplastin time (PTT) within normal limits. Patients receiving anti-coagulation treatment with an agent such as warfarin or heparin may be allowed to participate after discussion with ACORN. For patients on warfarin, the INR should be measured prior to initiation of sorafenib and monitored at least weekly, or as defined by the local standard of care, until INR is stable.
• Women of childbearing potential must have a negative serum or urine pregnancy test performed within 7 days prior to the start of treatment.
• Women of childbearing potential and men must agree to use adequate contraception (barrier method of birth control) prior to study entry and for the duration of study participation. Patients should use adequate birth control for at least 3 months after the last administration of sorafenib.
• Ability to understand and the willingness to sign a written informed consent. A signed informed consent must be obtained prior to any study specific procedures.

Exclusion Criteria:

• Prior use of bevacizumab.
• Neuropathy ≥Grade 2 per Common Terminology Criteria for Adverse Events Version 3.0 (CTCAE v3.0) [http://ctep.info.nih.gov/CTC3/ctc.htm].
• Diarrhea ≥Grade 2 per CTCAE v3.0 within 4 weeks of study treatment start.
• ECOG performance status ≥2.
• Proteinuria at baseline: patients discovered to have > 2+ proteinuria at baseline should undergo a 24 hour urine collection and must demonstrate < 1 gram of protein in 24 hours to be eligible.
• Active malignancy other than mCRC (except non-melanoma skin cancer; in situ carcinoma of the cervix; in situ carcinoma of the breast) within the last 5 years.
• Treatment with radiotherapy within 2 weeks of enrollment.
• Cardiac disease: Congestive heart failure >Class II New York Heart Association (NYHA) (see Appendix 3). Patients must not have unstable angina (anginal symptoms at rest) or new onset angina (began within the last 3 months) or myocardial infarction within the past 6 months.
• Known brain metastasis. Patients with neurological symptoms must undergo a computed tomography (CT) scan/magnetic resonance imaging (MRI) of the brain to exclude brain metastasis.
• Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy.
• Uncontrolled hypertension defined as systolic blood pressure >150 mm Hg or diastolic pressure >90 mm Hg, despite optimal medical management.
• Known human immunodeficiency virus infection or chronic Hepatitis B or C.
• Active clinically serious infection >Grade 2 per CTCAE v3.0.
• Thrombolic or embolic events such as a cerebrovascular accident including transient ischemic attacks within the past 6 months.
• Pulmonary hemorrhage/bleeding event ≥Grade 2 per CTCAE v3.0 within 4 weeks of study treatment start.
• Any other hemorrhage/bleeding event ≥Grade 3 per CTCAE v3.0 within 4 weeks of study treatment start.
• Serious non-healing wound, ulcer, or bone fracture.
• Evidence or history of bleeding diathesis or coagulopathy.
• Major surgery, open biopsy or significant traumatic injury within 4 weeks of study treatment start; fine needle aspiration or central venous line placement for chemotherapy administration within 7 days of study treatment start.
• Use of daily corticosteroids, St. John's Wort, rifampin (rifampicin), phenytoin, carbamazepine, phenobarbital, ketoconazole (see protocol section 5.1.3. CYP3A4 inducers and inhibitors). Dexamethasone may only be used as an antiemetic or as a premedication for a bevacizumab hypersensitivity reaction during participation in this study.
• Known or suspected allergy to sorafenib or any other agent given in the course of this trial.
• Any condition that impairs patient's ability to swallow whole pills.
• Any malabsorption problem.