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<i>Background and objectives</i>: This study aimed to evaluate prognostic factors for post-recurrence survival in local and locally advanced colorectal cancer patients. <i>Materials and Methods:</i> A total of 273 patients with stage III and high-risk stage II colorectal cancer were prospectively enrolled. All patients underwent operative treatment of the primary tumor and adjuvant fluorouracil-based chemotherapy. <i>Results:</i> Over the three-year period (2008–2010), a cohort of 273 patients with stage III and high-risk stage II colorectal cancer had been screened. During follow up, 105 (38.5%) patients had disease recurrence. Survival rates 1-, 3- and 5-year after recurrence were 53.9, 18.2 and 6.5%, respectively, and the median post-recurrence survival time was 13 months. Survival analysis showed that age at diagnosis (<i>p</i> < 0.01), gender (<i>p</i> < 0.05), elevated postoperative Ca19-9 (<i>p</i> < 0.01), tumor histology (adenocarcinoma vs. mucinous vs. signet ring tumors, <i>p</i> < 0.01) and tumor stage (II vs. III, <i>p</i> < 0.05) had a significant influence on post-recurrence survival. Recurrence interval and metastatic site were not related to survival following recurrence. Multivariate analysis showed that older age (HR 2.43), mucinous tumors (HR 1.51) and tumors expressing Ca19-9 at baseline (HR 3.51) were independently associated with survival following recurrence. <i>Conclusions:</i> Baseline patient and tumor characteristics largely predicted patient outcomes after disease recurrence. Recurrence intervals in local and locally advanced colorectal cancer were not found to be prognostic factors for post-recurrence survival. Older age, male gender, stage III and mucinous histology were poor prognostic factors after the disease had recurred. Stage II patients had remarkable post-recurrence survival compared to stage III patients.