Background: Both gemcitabine- and 5-FU-based chemotherapy (chemoRx) have demonstrated efficacy in MPC. Alternating these two regimens may 1) decrease toxicity 2) slow emergence of resistant cancer biology, and 3) provide a broader platform for addition of other (non)chemotherapeutic (CT) agents to the base regimen. The strategy using alternating G/A and FOLFIRI in MPC was first tested in the SEENA-1 trial (Picozzi et.al. GI Cancer Symposium 2017) and further suggested to be of benefit both at our own institution (Picozzi et.al. ASCO 2018) and elsewhere (Assenat et.al. ASCO 2018). We extend and update our observations here. Methods: Eligible patients (pts) had the following characteristics: 1) bx proven de novo MPC, 2) chemoRx naive, 3) ECOG PS 0/1, and 4) bi-dimensionally measurable disease. Treatment (Rx) consisted of 1) gemcitabine 1000 mg/m² and nab-paclitaxel 125 mg/²d 1,(8),15 alternating every 8 weeks (2 cycles) with FOLFIRI. Pts were radiographically restaged every 8 weeks. Rx was continued for up to 48 weeks, at which time additional Rx was given per physician/patient decision. Results: As of 9/2018, 61 pts have been treated at our institution via this method. Median age is 67; ECOG PS 0/1 58/42%. Disease site involvement included liver, lung, peritoneum 79%, 39%, and 23% respectively. Toxicity is less than typical with either individual regimen (e.g. no ≥ grade 3 neuropathy or diarrhea has been seen to date). Of pts followed for ≥ 4 months , 45/51 (88%) received ≥ 4 cycles Rx. Median number Rx cycles received was 9; 15/34 (44%) pts followed for > 1 year completed 48 weeks Rx. Disease control rate at 16 weeks in 45 evaluable patients is 89% (47% PR, 42% SD, 11% PD). 27/61 pts (44%) are currently on Rx (4 transferred care from region, 30 deceased). Currently, median f/u is 11.8 mo; median OS is 14.1 mo ( 95% CI 10.6-20.3 mo) 6,12, 18 and 24 mo OS are 88%,57 %, 34%, and 15% respectively. Conclusions: 1) Alternating G/A and FOLFIRI in MPC appears to have a more favorable toxicity profile than either individual regimen. 2) Median OS in MPC using this Rx is at least competitive with other reports. 3) The above method has potential to integrate other therapeutic agents/ treatment approaches.