Inclusion Criteria:
* Age: 18-75 years old.
* Unresectable esophageal squamous cell carcinoma confirmed by histopathology and/or cytology.
* Failure or intolerance to first-line treatment.
* At least one measurable lesion (according to RECIST v1.1).
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 \~ 1.
* The expected survival time ≥3 months.
* Subject has adequate biological parameters as demonstrated by the following: absolute neutrophil count (ANC) ≥1.5×10\^9/L, platelet count ≥100×10\^9/L, hemoglobin (Hgb) ≥90 g/L.
* Adequate hepatic function as evidenced by total bilirubin ≤1.5 × upper limit of normal (ULN), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 x ULN, ≤5 x ULN if liver metastases are present. Documented serum albumin ≥ 3 g/dL.
* Adequate renal function as evidenced by serum creatinine (Cr)≤1.5 x ULN or creatinine clearance ≥60 mL/min.
* Subjects agree to use contraception and are not pregnant or breastfeeding women.
* Agree and be able to comply with the plan during the study period. Provide written informed consent before entering the study screening.
Exclusion Criteria:
* Any other malignancy within 5 years prior to randomization, with the exception of cured in-situ carcinoma or basal cell carcinoma.
* Received irinotecan/irinotecan liposome based therapy in the first line.
* Active, uncontrolled bacterial, viral, or fungal infections that require systemic treatment.
* Active HIV infection.
* Combined with uncontrollable systemic diseases, such as unstable angina, myocardial infarction, congestive heart failure, severe unstable ventricular arrhythmia, severe pericardial disease history and other cardiovascular diseases; uncontrolled hypertension(Defined as systolic blood pressure≥140 mmHg and/or diastolic blood pressure≥90 mmHg after treatment with standardized antihypertensive drugs), or history of critical hypertension, hypertensive encephalopathy; uncontrollable diabetes, etc.
* Presence of severe gastrointestinal disease (including active bleeding, \> grade 1 obstruction , \> grade 1 diarrhea or gastrointestinal perforation)
* Allergy to or intolerance to therapeutic drugs or their excipients.
* Presence of central nervous system metastasis.
* Use of strong inhibitors or inducers of CYP3A, CYP2C8 and UGT1A1.
* Participated in other trial within 30 days or within 5 half-lives of the drug prior to the first dose of study treatment.
* Patients who are not suitable to participate in this trial for any reason judged by the investigator.
