Background: The benefit of adjuvant chemotherapy (ACT) following curative-intent surgery in pancreatic ductal adenocarcinoma (PDAC) patients who had received neoadjuvant modified FOLFIRINOX (mFOLFIRINOX) remains unidentified. This retrospective analysis aimed to assess the clinical relevance of ACT in patients who underwent surgery following neoadjuvant mFOLFIRINOX. Methods: Between January 2017 and December 2020, 220 patients received neoadjuvant mFOLFIRINOX and underwent pancreatectomy for localized PDAC at the Asan Medical Center, Seoul, Korea. Patients unable to undergo curative-intent surgical resection (R0 or R1) and those with histological types other than ductal adenocarcinoma were excluded. Survival outcomes were compared according to ACT administration. Disease-free survival (DFS) was defined as the duration between surgery and recurrence or death of any etiology, whichever occurred first; and overall survival (OS) was that between surgery and death from any etiology. Results: ACT was administered to 150 (68.2%) patients. ACT recipients were significantly younger (median age, 61 vs. 64, p = 0.035) and they received significantly fewer cycles of neoadjuvant chemotherapy (median, 7 vs. 9, p = 0.0001) compared to non-recipients. As ACT, mFOLFIRINOX (n = 98, 65.3%), gemcitabine monotherapy (n = 39, 26.0%), and gemcitabine-capecitabine (n = 4, 2.7%) were administered. ACT recipients showed significantly better survival outcomes compared to non-recipients; median DFS 13.4 months (95% CI, 10.7–18.8) vs. 8.3 months (95% CI, 4.9–16.0), respectively (p = 0.0042); and median OS 33.4 months (95% CI, 29.9–NA) vs. 23.8 months (95% CI, 17.9–NA), respectively (p = 0.0021). DFS and OS were significantly better in ACT recipients regardless of the lymph node (LN) status during surgery (p = 0.033 for DFS and p = 0.027 for OS in negative LN; and p = 0.032 for DFS and p = 0.012 for OS in positive LN). There was no significant difference in DFS (p = 0.79) and OS (p = 0.49) between mFOLFIRINOX and gemcitabine-based regimens. In multivariate analysis, ACT remained significant as a favorable prognostic factor (DFS, hazard ratio [HR] 0.43 (95%CI, 0.26–0.71, p = 0.001); OS, HR 0.33 (95%CI, 0.17–0.64, p = 0.001). Conclusions: In PDAC patients who underwent surgery following neoadjuvant mFOLFIRINOX, ACT may be associated with improved survival outcomes. Its benefit was not affected by the LN status and ACT regimens.