Nintedanib and Capecitabine in Treating Patients With Refractory Metastatic Colorectal Cancer

Inclusion Criteria:

* Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
* Hemoglobin \>= 9 g/dL
* Absolute neutrophil count \>= 1500/mm\^3
* Platelet count \>= 100,000/mm\^3
* Creatinine =\< 1.5 upper limit of normal (ULN) AND creatinine clearance (CrCl) \> 50 mL/min by Cockcroft-Gault equation
* Males = (140 -age (yrs) (body weight (kg)/(72) (serum creatinine) (mg/dL)
* Females = 0.85 \* (140-age (yrs) (body weight (kg)/(72)(serum creatinine (mg/dL)
* Bilirubin \< ULN
* Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =\< 1.5 ULN if without liver metastases
* AST/ALT =\< 2.5 x ULN if with liver metastases
* Coagulation parameters: international normalized ratio (INR) =\< 2, prothrombin time (PT) and partial thromboplastin time (PTT) \< 1.5 X institutional ULN
* Have measurable disease per RECIST 1.1 criteria
* Histologically or cytologically proven adenocarcinoma of the colon or rectum
* Prior progression following a fluoropyrimidine-based therapy and progression following or intolerance to irinotecan and oxaliplatin, as well as anti-epidermal growth factor receptor (EGFR) therapy (e.g., panitumumab or cetuximab) for rat sarcoma viral oncogene homolog (RAS) wild-type patients
* Ability to swallow and retain oral medication
* Participants of child-bearing potential must agree to use adequate contraceptive methods (e.g., hormonal or barrier method of birth control; abstinence) prior to study entry and for three months following completion of therapy; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
* Participant or legal representative must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure

Exclusion Criteria:

* Prior treatment with nintedanib
* Prior treatment with regorafenib
* Major injuries or surgery within the 4 weeks prior to initiation of therapy with incomplete wound healing or planned surgery during the on-study treatment period
* Uncontrolled hypertension: systolic blood pressure \>= 160, diastolic blood pressure \>= 90
* Urine protein/creatinine ratio \>= 1.0
* History of clinically significant hemorrhagic or thrombotic event within the past 6 months, not including uncomplicated catheter-associated venous thrombosis; patients on anti-coagulation are not permitted to be on any oral formulations (warfarin, rivaroxaban, dabigatran, etc.) due to concern for drug-drug interaction
* Unstable angina, symptomatic congestive heart failure or cardiac arrhythmia requiring anti-arrhythmic therapy (beta-blockers, calcium channel blockers and digoxin are allowed)
* History of cerebrovascular or myocardial ischemia within 6 months of initiation
* Known inherited predisposition to bleeding or thrombosis
* Known active or chronic hepatitis B or C or human immunodeficiency virus (HIV)
* Untreated brain metastases
* History of second primary malignancy diagnosed within 3 years prior to enrollment, excluding:

  * In-situ cervical carcinoma
  * Superficial bladder cancer
  * Non-melanoma skin cancer
  * Stage I breast cancer
  * Low grade (Gleason =\< 6) localized prostate cancer
  * Any additional malignancy which has been in clinical remission for at least 1 year
* Pregnant or nursing female participants
* Unwilling or unable to follow protocol requirements
* Any condition which in the Investigator's opinion deems the participant an unsuitable candidate to receive study drug
* Received an investigational agent within 4 weeks prior to enrollment
* PHASE I: History of intolerance to capecitabine at doses =\< 1000 mg/m\^2 BID, as defined by documented \>= grade 3 hand-foot syndrome, documented severe diarrhea requiring hospitalization, or other documented severe adverse events (AEs) attributable to capecitabine
* PHASE II: History of intolerance to capecitabine at doses below 1000 mg/m\^2 BID, as defined by documented \>= grade 3 hand-foot syndrome; documented severe diarrhea requiring hospitalization; or other documented severe AEs attributable to capecitabine