FOLFIRI or Modified FOLFIRI and Veliparib as Second Line Therapy in Treating Patients With Metastatic Pancreatic Cancer

Inclusion Criteria:

* Patients must have histologically or cytologically documented pancreatic adenocarcinoma; patients with pancreatic neuroendocrine tumors, lymphoma of the pancreas, or ampullary cancer are not eligible
* Patients must have metastatic disease that is measurable; computed tomography (CT) scans or magnetic resonance imaging (MRI)s used to assess measurable disease must have been completed within 28 days prior to registration; CT scans or MRIs used to assess non-measurable disease must have been completed within 42 days prior to registration; all disease must be assessed and documented on the Baseline Tumor Assessment Form
* Patients must not have history of brain metastases
* Patients must have had one and only one prior regimen of systemic therapy for metastatic disease unless the patient meets the criteria below
* Prior systemic therapy and chemoradiotherapy for treatment of resectable, borderline resectable or locally advanced unresectable disease is allowed and does not count toward prior therapy for metastatic disease
* Patients who received systemic therapy with gemcitabine/nab-paclitaxel for resectable or borderline/locally advanced unresectable disease and progressed with metastatic disease within 3 months of the past dose of systemic therapy are eligible
* Patients must have completed systemic therapy at least 14 days prior to registration, any surgical procedure must have been performed at least 14 days prior to registration, and radiation therapy must be completed at least 7 days prior to registration; patients must have recovered from major side effects of prior therapies or procedures in the opinion of the local site investigator prior to registration
* Patients must not have received prior irinotecan-based chemotherapy (e.g. irinotecan hydrochloride, leucovorin calcium, fluorouracil, and oxaliplatin \[FOLFIRINOX\] or FOLFIRI)
* Patients must not have received prior PARP inhibitor therapy including, but not limited to ABT-888, olaparib, rucaparib, and talazoparib (BMN637)
* Patients must have a Zubrod performance status of 0-1
* Within 14 days prior to registration: Absolute neutrophil count (ANC) \>= 1,500/mcL
* Within 14 days prior to registration: Hemoglobin \>= 9 g/dL
* Within 14 days prior to registration: Platelets \>= 100,000/mcL
* Within 14 days prior to registration: Total bilirubin =\< 1.5 x institutional upper limit of normal (IULN)
* Within 14 days prior to registration: Serum albumin \>= 3.0 g/dL
* Within 14 days prior to registration: Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 2.5 x IULN; patients with liver metastases may have AST and ALT of =\< 5.0 x IULN
* Within 14 days prior to registration: Serum creatinine =\< 2.0 mg/dL
* Patients must have CA19-9 obtained within 14 days prior to registration; if CA19-9 is normal a carcinoembryonic antigen (CEA) must be tested within 14 days prior to registration
* Patients must have blood urea nitrogen (BUN), alkaline phosphatase, sodium, potassium, calcium, glucose, chloride, and bicarbonate levels obtained within 14 days prior to registration
* Patients must not have any clinically significant and uncontrolled major medical condition(s) including, but not limited to uncontrolled nausea/vomiting/diarrhea; active uncontrolled infection; symptomatic congestive heart failure (New York Heart Association \[NYHA\] class \>= II); unstable angina pectoris or cardiac arrhythmia; psychiatric illness/social situation that would limit compliance with study requirements
* Patients must not have active seizure or history of seizure
* Patients must be able to swallow whole capsule
* Patients must have a complete physical examination and medical history within 28 days prior to registration
* Patients must not have known Gilbert's syndrome
* Patients must not have known hypersensitivity to irinotecan, fluorouracil, or leucovorin
* Patients of childbearing potential must have a negative pregnancy test within 28 days prior to registration and must not be nursing; women/men of reproductive potential must have agreed to use an effective contraceptive method during the study and for 6 months following completion of treatment; 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 be willing and able to undergo a biopsy after signed consent and prior to registration; patients must have tumor tissue and blood samples available and be willing to submit tumor and blood samples; NOTE: core biopsy required; fine needle aspiration (FNA) is not an acceptable substitute for core biopsy
* If archival tumor is available for submission, patients must be willing to submit tumor sample
* Patients must be offered the opportunity to participate in specimen banking for future use
* 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
* As a part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system