Irule Vs rewrite - FQDN hostname

There is no host header in the responses since it is a request header in http. So as long as you connect to the right ip and port of the backend server, and you have the correct host header in the request from F5 (since you handled that with the replace header command), you should get the answer from the server. This answer will then be sent to to the client from F5, and this should be transparent for the client unless you have some redirection happening in the server itself thats is redirecting to the real server name because F5 by default is forwarding these kind of redirections to the client. This can be checked on the client using F12 developer tools. If that is the case, there is solution for that (redirect rewrite)