Aflibercept and FOLFOX6 Treatment for Previously Untreated Stage IV Colorectal Cancer

Inclusion Criteria: * Histologically confirmed adenocarcinoma of colorectal origin that is metastatic or locally advanced and unresectable * Measurable disease, as defined by RECIST 1.1 criteria: one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as \>= 10 mm with spiral computed tomography (CT) scan (CT scan slice thickness no greater than 5 mm) malignant lymph nodes will be considered measurable if they are \>= 15 mm in short axis * Must not have received any prior systemic therapy for metastatic or locally advanced CRC; prior VEGF inhibitors are not allowed * Prior adjuvant therapy for CRC including fluoropyrimidines either alone or in combination with oxaliplatin is allowed, provided that all therapy was completed \>= 12 months from cancer recurrence, therapy duration was =\< 6 months, and all prior toxicities have completely resolved (residual grade 1 neuropathy is allowed) * Life expectancy \>= 12 weeks * Eastern Cooperative Oncology Group (ECOG) performance status 0-1 * Hemoglobin \>= 9 g/dL (blood transfusion permitted to attain this value) * Absolute neutrophil count \>= 1,500/uL * Platelets \>= 100,000/uL * Total bilirubin =\< 2 x institutional upper limit of normal (ULN) * Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase \[SGPT\]) =\< 2.5 x institutional ULN (may be =\< 5x ULN if increase is due to metastatic d…