A Study of Dulanermin Administered in Combination With the FOLFOX Regimen and Bevacizumab in Patients With Previously Untreated, Locally Advanced, Recurrent, or Metastatic Colorectal Cancer

Inclusion Criteria:

* Histologically confirmed CRC with evidence of locally advanced recurrent or metastatic disease (i.e., by radiographic imaging or biopsy) and measurable tumor lesions
* Life expectancy \> 3 months
* For patients of reproductive potential (males and females), use of reliable means for contraception throughout the trial
* Willingness and capability to be accessible for study follow-up

Exclusion Criteria:

* Prior 5-FU, capecitabine, and/or oxaliplatin treatment with the exception of: prior oxaliplatin treatment =\< 6 weeks in the advanced or metastatic setting; prior treatment with 5-FU, capecitabine, and/or oxaliplatin in the adjuvant setting if relapse occurred \> 6 months from concluding adjuvant therapy
* Peripheral neuropathy Grade \>= 2
* Prior radiotherapy to a measurable metastatic lesion(s) to be used for response assessment, unless the lesion has progressed subsequent to the radiotherapy
* Radiotherapy to a peripheral lesion within 14 days prior to Cycle 1, Day 1, or radiotherapy to a thoracic, abdominal, or pelvic field within 28 days prior to Cycle 1, Day 1
* Chemotherapy, hormonal therapy, or immunotherapy within 4 weeks prior to Cycle 1, Day 1
* Evidence of clinically detectable ascites
* Other invasive malignancies within 5 years prior to Cycle 1, Day 1
* Current or recent participation in another experimental drug study
* Clinically significant cardiovascular disease, New York Heart Association (NYHA) Grade II or greater congestive heart failure, serious cardiac arrhythmia within 1 year prior to Cycle 1, Day 1, or Grade II or greater peripheral vascular disease on Cycle 1, Day 1
* Active infection requiring parenteral antibiotics
* Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Cycle 1, Day 1, fine needle aspirations or minor surgery (such as port placement) within 7 days prior to Cycle 1, Day 1, or anticipation of need for major surgical procedure during the course of the study
* Known or suspected to be positive for the human immunodeficiency virus (HIV)
* Known to be positive for hepatitis C or hepatitis B surface antigen
* History of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates use of an investigational drug or specified study treatment, or that might affect interpretation of the results of the study or render the patient at high risk from treatment complications
* Inadequately controlled hypertension
* Prior history of hypertensive crisis or hypertensive encephalopathy
* History of arterial thromboembolic event 6 months prior to Cycle 1, Day 1
* History of abdominal fistula or gastrointestinal perforation within 6 months prior to Cycle 1, Day 1
* Bleeding diathesis or coagulopathy
* Pregnancy (positive pregnancy test) or breast feeding
* Serious, non-healing wound, ulcer, or bone fracture