Background: The immunoscore (IS), a prognostic score, was first validated in early colon cancer reflecting the immune response against the tumor. It showed potential in its ability to downstage patients with pathologic complete response (pCR) who would potentially benefit from organ-sparing therapies in locally advanced rectal cancer (LARC). We first presented our initial outcome with 37.8% pCR in patients with LARC treated with short course radiation therapy (SCRT) followed by 6 cycles of mFOLFOX plus Avelumab followed by total mesorectal excision (TME) in the ESMO 23rd World Congress on Gastrointestinal Cancer 2021 Conference (presentation # SO-30). Here we are reporting the post-hoc analysis of the correlation between pCR and pre-treatment biopsy IS to further establish the IS as a prognostic score in patients with LARC. Methods: In this Phase II study, 44 patients were accrued from three centers, of whom 40 completed radiotherapy followed by chemoimmunotherapy then TME. 39 patients with available tissue samples, containing tumor cells and its margins, were collected at baseline. CD3 and CD8 cells were counted, and the IS is then derived from the mean density percentiles of CD3 and CD8 positive T cells infiltrating the tumor and in the invasive margin of the tumor. Cutoff for a high IS was established at 62%. We then compared the tumor regression grade (TRG) with the means of IS, using the student t-test. Results: 15 patients with pCR had a mean IS of 68 +/- 22 SD as opposed to a mean IS of 52 +/- 22 SD in 24 patients without pCR (p = 0.036). Conclusions: High IS correlates with TRG as pCR and successfully predicted clinical outcome in LARC patients who underwent chemoimmuno-therapy. It is a promising potential prognostic tool in stratifying patients who would benefit from specific modalities to augment pCR and subsequent organ preservation strategy. Clinical trial information: NCT03503630.