Inclusion Criteria:

          -  Patients must have histologically or cytologically confirmed small bowel
             adenocarcinoma. Ampullary adenocarcinomas are not eligible. Patients must have
             metastatic disease or locally advanced unresectable disease

          -  Brain metastases are allowed if they have been adequately treated with radiotherapy or
             surgery and stable for at least 30 days prior to registration. Patients must be
             neurologically asymptomatic and without corticosteroid treatment for at least 7 days
             prior to registration

          -  Patients must have measurable or non-measurable disease. All scans needed for
             assessment of measurable disease must be performed within 28 days prior to
             registration. Non-measurable disease must be assessed within 42 days prior to
             registration. All disease must be assessed and documented on the Baseline Tumor
             Assessment Form

          -  Patients must have progressed on prior therapy with a fluoropyrimidine and/or
             oxaliplatin, given either for metastatic/locally advanced disease or as adjuvant
             therapy completed within the previous 12 months

          -  Patients must have completed prior chemotherapy, immunotherapy, or radiation therapy
             at least 14 days prior to registration and all toxicity must be resolved to grade 1
             (with the exception of grade 2 neuropathy) prior to registration. In Common
             Terminology Criteria for Adverse Events (CTCAE) version 5.0 grade 2 sensory neuropathy
             is defined as "moderate symptoms; limiting instrumental activities of daily living
             (ADLs)"

          -  Patients must have a complete medical history and physical exam within 28 days prior
             to registration

          -  Patients must have a Zubrod performance status of 0 or 1

          -  Absolute neutrophil count (ANC) >= 1,500/mcL (must be obtained within 28 days prior to
             registration)

          -  Platelets >= 100,000/mcL (must be obtained within 28 days prior to registration)

          -  A total bilirubin =< 1.5 x institutional limit normal (IULN) (must be obtained within
             28 days prior to registration)

          -  Serum glutamic-oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) and
             serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 3.0 x
             IULN (or 5.0 x IULN if liver metastases are present) (must be obtained within 28 days
             prior to registration)

          -  Serum creatinine =< 1.5 x IULN OR calculated creatinine clearance >= 40 mL/min (must
             have been obtained within 28 days prior to registration)

          -  Patient must have urinary protein =< 1+ on dipstick or routine urinalysis (UA) within
             28 days prior to registration. If dipstick or routine analysis is >= 2+, a 24 - hour
             urine collections for protein must demonstrate < 1000 mg of protein in 24 hours

          -  Patients with a prior or concurrent malignancy whose natural history or treatment does
             not have the potential to interfere with the safety or efficacy assessment of the
             investigational regimen are eligible for this trial

          -  Patients must not have known dihydropyrimidine dehydrogenase deficiency

          -  Patients must be offered the opportunity to participate in specimen banking

          -  Patients must be informed of the investigational nature of this study and must sign
             and give written informed consent in accordance with institutional and federal
             guidelines

        Exclusion Criteria:

          -  Patients must not have received prior treatment with irinotecan, taxane, or
             ramucirumab for small bowel adenocarcinoma

          -  Patients must not have had major surgery within 28 days prior to registration, or
             minor surgery within 7 days prior to registration, and must not be planned for
             elective major surgery to be performed during protocol treatment

          -  Patients must not be currently enrolled in or have discontinued within the last 28
             days a clinical trial involving an investigational product or non-approved use of a
             drug, or concurrently enrolled in any other type of medical research judged not to be
             scientifically or medically compatible with this study. Patients participating in
             surveys or observational studies are eligible to participate in this study

          -  Patients must not be receiving chronic antiplatelet therapy, including dipyridamole or
             clopidogrel, or similar agents

          -  Patient must not have a known bleeding diathesis

          -  Patient must not have uncontrolled or poorly-controlled hypertension (> 160 mmHg
             systolic or > 100 mg HG diastolic for > 4 weeks) despite standard medical management

          -  Patient tumors must not have known deficient mismatch repair (dMMR) or microsatellite
             instability high (MSI-H)

          -  Patients must not be pregnant or nursing and must have had a negative pregnancy test
             within 4 weeks of starting treatment. Women/men of reproductive potential must have
             agreed to use an effective contraceptive method. A woman is considered to be of
             "reproductive potential" if she has had menses at any time in the preceding 12
             consecutive months. In addition to routine contraceptive methods, "effective
             contraception" also includes heterosexual celibacy and surgery intended to prevent
             pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy,
             bilateral oophorectomy or bilateral tubal ligation. However, if at any point a
             previously celibate patient chooses to become heterosexually active during the time
             period for use of contraceptive measures outlined in the protocol, he/she is
             responsible for beginning contraceptive measures

          -  Patients must not have an active infection requiring systemic therapy

          -  Patient must not have liver dysfunctions manifested by either (1) Child-Pugh B (or
             worse) or (2) cirrhosis (any degree) and a history of hepatic encephalopathy or
             clinically meaningful ascites resulting from cirrhosis. Clinically meaningful ascites
             is defined as ascites from cirrhosis requiring diuretics or paracentesis

          -  Patients must not have a history of deep vein thrombosis (DVT), pulmonary embolism
             (PE), or any other significant thromboembolism (venous port or catheter thrombosis or
             superficial venous thrombosis are not considered "significant") during the 90 days
             prior to registration

          -  Patients must not have experienced any arterial thrombotic event (including but not
             limited to myocardial infarction, unstable angina, stable angina markedly limiting
             ordinary physical activity, cerebrovascular accident, or transient ischemic attack)
             within 120 days prior to registration

          -  Patients must not have a prior history of gastrointestinal (GI) perforation/fistula or
             other risk factors for perforation within 120 days prior to registration

          -  Patients must not have experienced any grade 3-4 GI bleeding within 90 days prior to
             registration

          -  Patient must not have experienced any serious or non-healing wound, ulcer, or bone
             fracture within 28 days prior to registration