Background: At presentation only 20% of pancreatic cancer patients are defined resectable due to advanced initial disease stage. Objective: To study the clinical outcome of patients with unresectable locally advanced ‎pancreatic cancer (LAPC) after neoadjuvant modified FOLFIRINOX-losartan ‎followed by chemoradiotherapy. Methods: This phase II clinical trial was carried out on 50 patients with newly diagnosed surgically unresectable LAPC. Patients had Performance status (PS) ≤ 1 and normal organ functions. They arranged to receive 3 cycles of modified FOLFIRINOX with losartan taken orally every day followed by chemoradiotherapy (CCRT). Results: Out of the 50 patients, thirteen (26%) patients had surgery; R0 resection achieved in 6 of 13 patients. After median follow-up duration of 20.25 months (6.0-34.5 months), the median overall survival (OS) was 21 months (95% CI, ‎(10.200–31.800). Patients who had surgical resection had longer OS of 24 months (95% CI, ‎ (16.363 – 27.637) compared to those who didn't have resection the mean OS was 14 months (95% CI, (9.205 – 18.795) (P=0.271). The patients who achieved CR after modified FOLFIRINOX had longer survival of 33 months (95% CI, 19.918 – 46.082) compared to those who had PR and SD. Each has median OS of 13 months (95% CI, 6.768 – 19.232), (11.718 – 14.282) respectively (P=0.040*). The patients who achieved CR after CCRT had longer OS (median not reached) compared to those who had PR, SD and PD; median OS was 24, 14 and 8 months respectively and 95% CI was (6.761 – 41.239), (11.022 – 16.978), and (4.080 – 11.920) respectively (P=0.001*). Conclusion: Modified-FOLFIRINOX/losartan protocol followed by CCRT had high response, feasible and could improve patients' outcomes in LAPC.