Handbook and Reference manual

Handbook noun - A book used for instruction in a subject.

Reference manual and handbook are semantically related in guide topic. In some cases you can use "Reference manual" instead a noun "Handbook", when it comes to topics like manual, reference book.

Reference manual noun - A manual containing information organized in a summary manner.

Handbook and reference manual are semantically related in guide topic. You can use "Handbook" instead a noun phrase "Reference manual", if it concerns topics such as reference book.