If you update or create a CDS record, lookups are required to contain a valid GUID. So it's not possible to populate lookups with null. When updating/creating all lookups need to be filled, it's not possible for a user to leave lookups empty. You can solve this by conditionally updating the record (only update when the lookup field contains data), but this is not workable with multiple lookups on a record.
It would be great if a null value would be accepted in a lookup, so the flow knows to ignore and not update the lookup field.