Background: Refractory metastatic colorectal cancer patients (mCRC) have a poor prognosis with median survival of 4-6 months. Nintedanib is a TKI which inhibits VEGFR, PDGFR, and FGFR with preclinical efficacy in bevacizumab resistant CRC. This phase I/II study sought to evaluate the recommended phase II dose (RP2D) and efficacy of nintedanib and capecitabine in refractory mCRC patients. Methods: Key eligibility criteria included histologically proven mCRC, ECOG PS of 0 or 1, progression/intolerance to a fluoropyrimidine, oxaliplatin, irinotecan, and anti-EGFR therapy for RAS wt patients. Prior regorafenib, uncontrolled hypertension ( ≥ 160/90), recent clinically significant thrombosis/hemorrhage, or prior intolerance to capecitabine were exclusionary. Doses were escalated across 2 planned dose levels (DL) in a standard 3+3 design, with escalating doses of capecitabine. DLT observation window was the first 3 weeks after dosing. The primary endpoint was establishment of the RP2D. Results: 10 patients were enrolled across 2 dose levels. 1 patient withdrew consent and was replaced. 5 (50%) were PS 0. No grade 4 or 5 AEs were observed. No DLTs were observed. 2/10 (20%) of patients experienced a grade 3 AE, including hyperbilirubinemia (10%), AST elevation (10%), diarrhea (10%), dehydration (10%), and weakness (10%). The most common treatment-related AEs included palmar-plantar eythrodysesthesia (PPE) (50%), diarrhea (40%), stomatitis (30%), nausea (20%), vomiting (20%), and fatigue (20%). The RP2D was determined to be capecitabine 1000 mg/m2 divided bid and nintedanib 200 mg bid. PK data will be presented. Conclusions: Treatment was well tolerated. Most of the observed AEs were grade 1 or 2, without a marked difference between DLs. PPE was readily managed with dose adjustments. The phase II study is ongoing at the RP2D. This study was approved and funded by the National Comprehensive Cancer Network (NCCN) Oncology Research Program from general research support provided by Boehringer Ingelheim Pharmaceuticals, Inc. Clinical trial information: NCT02393755