Background: F-NOX is increasingly utilized in BRPC as neoadjuvant therapy. However, prospective data remains limited; the largest series is a 22 patient (pt) cooperative group trial (Alliance A021101), in which 14 pts had R0 resection. In this study, we evaluate neoadjuvant F-NOX followed by individualized chemoradiation (CRT) for BRPC. Methods: Pts ECOG PS 0-1 with biopsy-proven BRPC defined by NCCN criteria were enrolled in a single institution, NCI-sponsored phase II study (NCT01591733). Pts received F-NOX for 8 cycles. If after chemotherapy the tumor was radiographically resectable, pts received short course CRT in 5 (protons 25 GyE) or 10 fractions (photons 30 Gy) with capecitabine 825 mg/m2 bid. If the tumor was still abutting vasculature, pts received CRT to 50.4 Gy with a vascular boost to 58.8 Gy. Primary endpoint was R0 resection rate. Results: 50 pts were enrolled from 8/2012 to 8/2016. Two pts were ineligible (lung metastasis, negative biopsy); 48 pts were evaluable. Median age was 62y (46-74). Median tumor size was 37 mm (21-56). Thirty-six pts (75%) had pancreatic head tumors. Median follow up was 18.2 months among 31 patients still alive. Of the evaluable pts, 40 (83%) completed therapy. Reasons for not completing therapy include pt withdrawal (3), physician decision (3), unacceptable toxicity (1) and progression (1). Grade 3 or greater toxicity occurred in 48% of pts, but no individual grade 3 toxicity exceeded 15%. Twenty-seven pts (56%) had short course CRT, while 13 pts (27%) had long course CRT. Twenty-nine pts were resected; R0 resection was achieved in 28/29 (96.5%). R0 resection rate among all evaluable pts was 58.3%. Median PFS among all evaluable pts was was 14.7 months; mOS was 37.7 months, with 1y OS 79.5% and 2y OS 59.3%. Among resected patients, mOS has not been reached. 1y PFS was 78.1% and 2y PFS 55.4%; 1y OS was 92.6% and 2y OS was 80.6%. Conclusions: Preoperative F-NOX followed by individualized chemoradiation in BRPC results in high R0 resection rates as well as prolonged mPFS and mOS in this large prospective cohort. Clinical trial information: NCT01591733