A Study Combining mFOLFOX6 With Tivozanib or Bevacizumab in Patients With Metastatic Colorectal Cancer as First Line Therapy

Inclusion Criteria:

* Documented diagnosis of metastatic colorectal cancer
* One measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
* No prior systemic chemotherapy for advanced colorectal cancer; no fluorouracil containing adjuvant therapy in previous 6 months
* Eastern Cooperative Oncology Group (ECOG) status of 0 or 1

Exclusion Criteria:

* Any prior Vascular Endothelial Growth Factor (VEGF)-directed therapy or any other agent or investigational agent targeting the VEGF pathway
* Primary Central Nervous System (CNS) malignancies or CNS metastases
* Hematologic abnormalities:

  * Hemoglobin \< 9.0 g/dL,
  * Absolute neutrophil count (ANC) \< 2000 per mm\^3,
  * Platelet count \< 100,000 per mm\^3,
  * Prothrombin (PT) or Partial Thromboplastin Time (PTT) \> 1.5 X Upper Limit of Normal (ULN)
* Serum chemistry abnormalities:

  * Total bilirubin \> 1.5 X ULN,
  * Aspartate aminotransferase (AST) or Alanine Aminotransferase (ALT) \> 2.5 X ULN,
  * Alkaline phosphatase \> 2.5 X ULN,
  * Serum albumin \< 2.0 g/dL,
  * Creatinine \> 1.5 X ULN,
  * Proteinuria \> 2+ by urine dipstick
* Significant cardiovascular disease
* Significant thromboembolic or vascular disorders within 6 months prior to administration of first dose of study drug
* Non-healing wound, bone fracture, or skin ulcer
* Inadequate recovery from any prior surgical procedure or major surgical procedure within 8 weeks prior to administration, or anticipation of major surgical procedure during the course of the study
* History of significant gastrointestinal (GI) toxicity, diarrhea, or stomatitis within the last 6 weeks
* An active peptic ulcer disease, inflammatory bowel disease, ulcerative colitis, or other gastrointestinal condition with increased risk of perforation
* History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 4 weeks prior to administration of first dose of study drug
* Serious/active infection or infection requiring antibiotics
* Significant bleeding disorders within 6 months prior to administration of first dose of study drug
* Active second primary malignancy, other than non-melanoma skin cancers, non-metastatic prostate cancer, in situ cervical cancer and ductal or lobular carcinoma in situ of the breast. Subject is not considered to have a currently active malignancy if they have completed anti-cancer therapy and have been disease free for \> 5 years
* History of allergic reactions, or intolerance, attributed to compounds of similar chemical or biologic composition to 5-fluorouracil, history of Grade 3 hypersensitivity to oxaliplatin, history of allergic reaction to folic acid
* Female subject is pregnant or lactating
* Known history of genetic or acquired immune suppression disease including Human Immunodeficiency Virus (HIV); subjects on immune suppressive therapy for organ transplant
* Inability to swallow pills, malabsorption syndrome or gastrointestinal disease, major resection of the stomach or small bowel, or gastric bypass
* Uncontrolled neuro-psychiatric disorder or altered mental status
* Peripheral neuropathy ≥ Grade 2
* Participating in another interventional protocol