Short-Infusion Ziv-aflibercept in Treating Patients With Metastatic Colorectal Cancer Receiving Combination Chemotherapy

Inclusion Criteria:

* Patients with metastatic colorectal cancer are eligible for this study; colorectal cancer should have been previously confirmed by pathology or cytology; to be eligible for this protocol, patients should be receiving ziv-aflibercept plus FOLFIRI as a standard treatment prior to enrolling on this trial; the number and type of therapy administered prior to enrollment will not affect the ability to enroll on this study
* Patients should have an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
* Patients should have an expected life expectancy of 12 weeks or longer
* Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control or abstinence) prior to study entry and for six months following duration of study participation; should a woman become pregnant or suspect that she is pregnant while participating on the trial, she should inform her treating physician immediately
* To be eligible for this study, patients should already be receiving a standard dose of ziv-aflibercept intravenously over 60 minutes in combination with FOLFIRI chemotherapy every 2 weeks without evidence of progressive disease; treatment on this study can start as early as two weeks from last "off protocol" ziv-aflibercept plus FOLFIRI cycle, granted treatment parameters have been met
* Total bilirubin \< 1.5 upper limit of normal (ULN)
* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \< 3 ULN unless patient has metastatic disease to the liver in which case \< 5 ULN will be allowed
* Serum creatinine \< 1.5 ULN
* Urine protein/creatinine ration (UPCR) =\< 1 or total urinary protein of \< 1 gm/24 hours in the event the UPCR \> 1
* Systolic blood pressure \< 155 mm mercury and diastolic blood pressure \< 100 mm mercury documented on two separate occasions at least 24 hours apart
* Platelet counts \>= 75,000/mm\^3
* Neutrophil count \>= 1500/mm\^3
* Hemoglobin \>= 9 gm/dl; anemia can be corrected with transfusion to allow eligibility prior to enrollment
* Hematological tests can be repeated to assess eligibility
* No unresolved grade 2 or above non-hematological toxicities, with the exception of alopecia or neuropathy
* All subjects must have the ability to understand and the willingness to sign a written consent

Exclusion Criteria:

* Patients should not have any uncontrolled illness such as congestive heart failure, respiratory distress, and including ongoing or active infection
* Patients may not be receiving any other investigational agents, or concurrent biological, chemotherapy, or radiation therapy with the exception of study drugs
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to ziv-aflibercept
* Patients should be at least 2 weeks from their last dose of ziv-aflibercept when they receive their first dose of study treatment
* Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated on this study
* Patients with other active malignancies are ineligible for this study with the exception of non-melanoma skin cancer that is amenable to excision, cervical carcinoma in situ, hormone sensitive prostate cancer, or prostate cancer with no measurable disease (watchful waiting)
* History of arterial thrombotic events within 1 year prior to enrollment on study
* Surgical intervention within 4 weeks prior to study initiation and no open wounds
* Clinically significant bleeding; clinically significant bleeding is defined as gastrointestinal bleeding requiring a blood transfusion, bleeding manifesting as melena, or blood per rectum estimated to exceed 2 tablespoons within 4 weeks prior to enrollment; hemoptysis associated with blood loss of more than 1/2 tablespoon per day is also considered significant; physician judgment will be used to estimate presence or lack of significant clinical bleeding
* History of bowel perforation
* History of intracranial bleeding
* History of reversible posterior leukoencephalopathy syndrome (RPLS)
* History of active fistula
* Subjects, who in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study will be excluded