pMMR/MSS and 32 dMMR/MSI-H patientspatients were planned to be enrolled. Patients with dMMR/MSI-H will be randomly assigned to the immunotherapy arm or short-course radiotherapy sequential immunotherapy arm; pMMR/MSS patients will receive capecitabine-irinotecan based concurrent radiotherapy before being randomly assigned to the XELIRI or FOLFRINOX arm.

The rate of complete response (sustained cCR for ≥ 1 year), long-term prognosis and adverse effects will be analyzed.

Inclusion Criteria:

1. pathological confirmed adenocarcinoma；
2. clinical stage T2-4 and/or N+，Not suitable for initial local excision to achieve radical treatment；
3. the distance from anal verge less than ≤ 5cm，or surgical evaluation concludes that direct surgical anal preservation is not possible without distance metastases；
4. age 18-70 years old, female and male；
5. Strong desire for anal preservation and ability to be closely monitored for at least 2 years after chemoradiotherapywith good compliance；
6. without distant metastases；
7. ECOG Performance status 0-1；
8. Detection of UGT1A1*6 and *28 gene status (for pMMR patients)；
9. Sufficient bone marrow reserve and physical capacity to receive consolidation chemotherapy after chemoradiotherapy (for pMMR patients)；
10. with good compliance；
11. signed the inform consen.

Exclusion Criteria:

1. pregnant or breastfeeding women；
2. Persons with a history of uncontrolled epilepsy, central nervous system disorders, or psychiatric disorders whose clinical severity, as judged by the investigator, may prevent the signing of informed consent or affect the patient's compliance with oral medications；
3. Difficult to achieve complete remission at the available level of evidence, such as: tumor largest diameter >10 cm; largest diameter of lateral lymph nodes >2 cm; baseline CEA >= 100; biopsy pathology with an indolent cell carcinoma component; tumor of circumferential narrowing type on anal finger examination, with inclusion decided by the judgment of the evaluation team if necessary；
4. Clinically significant (i.e., active) heart disease, such as symptomatic coronary artery disease, New York Heart Association (NYHA) class II or worse congestive heart failure or severe arrhythmias requiring pharmacological intervention, or a history of myocardial infarction within the last 12 months；
5. persons requiring immunosuppressive therapy for organ transplantation；
6. Persons with severe uncontrolled recurrent infections, or other severe uncontrolled concomitant diseases；
7. Subjects with baseline routine blood and biochemical indicators do not meet the following criteria: hemoglobin ≥ 90g/L; absolute neutrophil count (ANC) ≥ 1.5×109/L; platelets ≥ 100×109/L; ALT, AST ≤ 2.5 times the upper limit of normal; ALP ≤ 2.5 times the upper limit of normal; serum total bilirubin < 1.5 times the upper limit of normal; serum creatinine < 1 times the upper limit of normal limit; serum albumin ≥30g/L；
8. Known to have dihydropyrimidine dehydrogenase (DPD) deficiency；
9. allergic to any investigational drug component.