Background: FOLFIRINOX is an active regimen for metastatic pancreatic cancer demonstrating a median overall survival of 11.1 months at the expense of significant treatment-related toxicity. Dose modifications are routinely used in clinical practice however there is little data regarding impact on outcomes and use of second line therapy. In this study we report on the treatment course and outcomes of 92 patients treated at two academic centers. Methods: We conducted an IRB-approved retrospective cohort study of patients with metastatic pancreatic adenocarcinoma treated with first line FOLFIRINOX between 2011 and 2015. Hazard ratios were calculated by Cox proportional hazard models and median survival was estimated using Kaplan-Meier method. Results: 92 patients were identified with a median follow-up of 13.2 months (range 1.2-47.3 mo); 57 males (62%), ECOG 0/1 = 75 (82%). Fifty-four percent required dose reductions of >25% in at least one of three component drugs within the first 6 cycles [95% CI 0.44, 0.65]. Irinotecan was dose reduced in 43% of patients (n=39) while 64% required modification or discontinuation of 5FU. Ten patients (11%) received the full dose of FOLFIRINOX as originally published and 17 patients (25%) discontinued FOLFIRINOX due to toxicity. 60% of patients demonstrated disease control at first imaging assessment after 4-6 cycles of treatment. Median PFS was 7.11 months (95% CI: 5.06-8.51) and OS 13.01 months (95% CI: 9.17-16.95). There was a decrease in PFS and OS associated with a dose reduction of two or more drugs with a HR of 1.68 (95% CI 1.01-2.82, p=0.048) and 1.98 (95% CI 1.08-3.65, p=0.027) respectively. Sixty-seven patients [73%] went on to receive 2^nd line therapy [n=67] with 55% receiving gemcitabine-based regimens, the majority with nab-paclitaxel [82%]. Forty-two patients demonstrated progressive disease [63%]. Conclusions: Modest FOLFIRINOX dose modifications are prevalent in clinical practice and are not associated with a reduction in efficacy. A median survival of 13 months with dose modified FOLFIRINOX is compelling. Dose reduction of 2 or more agents was associated with diminished survival. Second line therapy following FOLFIRINOX was associated with modest activity.